Researchers in Cairo have successfully demonstrated the ability of adult stem cells derived from bone marrow to treat cardiac dysfunction that is secondary to diabetes in a rat model.

Previously, adult mesenchymal stem cells (MSCs) derived from bone marrow have already been used for the treatment of a number of non-hematopoietic diseases, such as for various cardiac, liver and kidney conditions, among other ailments. Now, however, Dr. Abdel Aziz and his colleagues in the Department of Medical Biochemistry in the Faculty of Medicine at Cairo University have published the results of a study investigating the effects of MSCs on cardiovascular complications resulting from Type 1 diabetes in rats. The study is unique because it is the first of its kind to offer an adult stem cell treatment for chronic cardiac dysfunction, which is significantly different from cardiac dysfunction that is caused by an acute event such as a heart attack. Following an acute cardiac event or injury, the body normally releases therapeutic chemokines which stimulate the homing action of endogenous stem cells and which also play a role in enhancing the efficacy of exogenously administered stem cells. In the current study, such naturally occurring chemokines and their corresponding healing action were not part of the therapy.

In the study, MSCs were derived from the bone marrow of male albino rats and infused into female diabetic rats. Serum insulin, glucose and fibrinogen were estimated and physiological cardiovascular functions such as heart rate and systolic blood pressure were assessed by a Langendorff apparatus. At the conclusion of the study, not only had cardiac and diabetic conditions both improved, but Y-chromosome positive cells were found in the both the cardiac and pancreatic tissue of the female recipient rats, demonstrating that the observable therapeutic effects were in fact the result of the male stem cells.

As Dr. Aziz and his colleagues concluded, “Rat bone marrow harbors cells that have the capacity to differentiate into functional insulin-producing cells capable of controlling blood glucose levels in diabetic rats. This may provide a source of cell-based therapy for diabetes mellitus. Furthermore, MSC transplantation can improve cardiac function in diabetes mellitus.”

The U.S. company Advanced Cell Technology (ACT) and the South Korean company CHA Biotech Ltd. have announced the formation of new company that is the product of a joint venture. The new company is to be known as “Stem Cell and Regenerative Medicine International” and will be headquartered in Worcester, Massachusetts, the site of one of ACT’s laboratories and former headquarters.

CHA Biotech, which is based in Seoul, operates a cord blood bank known as CHA i-Cord in addition to an active regenerative medicine R&D facility. Similarly, ACT is well known for a number of accomplishments in regenerative medicine, especially for their development of the hemangioblast cell technology. In the new partnership, both companies will collaborate together as one new company in the further development and commercialization of proprietary stem cell technology and cell-based clinical therapies. Under the agreement, the new company will be majority owned by CHA, to whom ACT will exclusively license all of its hemangioblast technology. Hemangioblasts are precursor cells with the ability to differentiate into both hematopoietic and endothelial cell lineages, and are found in embryonic tissue as well as in the tissue and circulating stem cells in the peripheral blood of adults.

Operating the largest stem cell research institute in Korea, CHA Biotech was founded in 2000 to develop gene therapy in addition to stem cell therapies. In 2002 the company expanded into the U.S. by opening the CHA Fertility Center in Los Angeles, which was followed in 2005 by the acquisition of the Hollywood Presbyterian Medical Center, an acute-care hospital in Los Angeles.

Advanced Cell Technology is involved in both embryonic and adult stem cell research. Its Myoblast technology consists of an autologous adult stem cell therapy designated for the treatment of heart disease which has successfully completed four Phase I clinical trials and has FDA clearance to begin Phase II trials. In addition, ACT is developing its RPE (retinal pigment epithelial cell) program for the treatment of retinal degenerative disorders, and its HG (hemangioblast) cell program for the treatment of blood disorders, cardiovascular disease, stroke and cancer.

Since August of 2006, when ACT announced a novel technique for generating embryonic stem cell lines without destroying the embryos, the company has announced on several occasions the creation of human embryonic stem cell lines that did not involve the destruction of embryos. Currently ACT owns or licenses over 380 patents and patent applications, and continues to operate laboratories both in Massachusetts and California, even though it moved its headquarters from Worcester, Massachusetts to Los Angeles in 2006 in order to take advantage of the $3 billion stem cell research initiative that was voted into state law in California with the passing of Proposition 71 in 2004.

The accelerating pace of international joint ventures is merely another indication of the rapid globalization of biotechnology, especially in the field of regenerative medicine, which has the potential to change the fundamental nature of health care and medical treatment for everyone on the planet. Along those lines, ACT’s chief scientific officer and head of the joint venture, Dr. Robert Lanza, was featured in a television special with Barbara Walters entitled, “Live to be 150 – Can You Do It?”, which was broadcast in the U.S. in April of 2008.

Osiris Therapeutics announced today that it has received $5 million in payment for having reached the first production threshold of the Osteocel supply agreement with NuVasive. In a business deal that was valued at $85 million, Osiris sold Osteocel, its bone matrix product, to the San Diego-based spine specialization company NuVasive Inc. in July of 2008 for an initial payment of $35 million which is to be followed by further payments totalling an additional $50 million when milestones are reached.

According to NuVasive chairman and CEO Alex Lukianov, “Osteocel provides what we believe to be one of the more powerful biologic platforms on the market today.” Osiris CFO Richard Hunt adds, “It is through the hard work and dedication of our Osteocel team that we have achieved the first product supply milestone under the agreement and are solidly on track to hit the remaining milestones. With more than 15 years of rigorous stem cell research and development behind it, today Osteocel stands alone in orthopedics. Along with our excellent partners at NuVasive, we look forward to the product’s continued success.”

A leader in adult stem cell therapies, Osiris Therapeutics is focused on the development of products for the treatment of inflammatory, orthopedic and cardiovascular diseases. One of its proprietary adult stem cell products, Prochymal, is currently in Phase III clinical trials for the treatment of Graft-versus-host disease and Crohn’s disease, and is also being evaluated for the repair of heart attack damage, the protection of pancreatic beta islet cells in patients with type 1 diabetes, and for the treatment of chronic obstructive pulmonary disease. Another product, Chondrogen, is currently undergoing evaluation for the treatment of arthritis in the knee. With an extensive intellectual property portfolio containing 47 patents, Osiris has formed a partnership with Genzyme Corp. for the development and commercialization of Prochymal and Chondrogen in countries outside of the U.S. and Canada.

In a series of experiments that are founded upon the success of Genzyme’s proprietary drug, Mozobil (see “Genzyme Receives FDA Approval for Mozobil”, December 15, 2008), scientists at the Imperial College of London have demonstrated the unsuspected regenerative potency of endogenous, autologous adult stem cells.

A novel, proprietary small-molecule CXCR4 chemokine receptor agonist, Mozobil is designed for use with G-CSF (granulocyte-colony stimulating factor) and has already received FDA marketing approval in the treatment of non-Hodgkin’s lymphoma and multiple myeloma. By stimulating the migration of hematopoietic stem cells from the bone marrow into the bloodstream for subsequent collection and autologous stem cell transplantation, Mozobil has already been shown to play an important role in the treatment of plasma and hematologic cancers. Now, however, researchers at the Imperial College of London have demonstrated for the first time that the regenerative power of autologous adult stem cells is not limited only to blood cells but also extends to the regeneration of other tissue, such as bone and blood vessels.

According to Dr. Sara Rankin, who led the study at the Imperial College of London, “It’s promoting self-healing. We’re simply boosting what’s going on naturally.”

The experiments were conducted with a mouse model in which Dr. Rankin and her colleagues selectively administered Mozobil in combination with either of the natural growth factors G-CSF or VEGF (vascular endothelial growth factor). When combined with VEGF, Mozobil was found to stimulate mesenchymal stem cells (MSCs) which differentiate into bone and other tissue types, as well as endothelial progenitor cells which differentiate into blood vessels. By contrast, G-CSF, which is known to stimulate the mobilization of hematopoietic stem cells, was found not to stimulate the production of MSCs. Similarly, VEGF was found not to stimulate hematopoietic stem cell mobilization. The degree to which stem cell mobilization increased was particularly dramatic, as mice that received VEGF in combination with Mozobil were found to release approximately 100 times as many endothelial and mesenchymal stem cells into the bloodsteram when compared to control mice who did not receive the treatment.

This is the first concrete evidence that different mechanisms of stimulation release different, specific types of stem cells. As Dr. Robert Lanza, chief scientist at Advanced Cell Technology in Worcestor, Massachusetts, explains, “The ability to selectively stimulate a patient’s own stem cells could be a powerful tool for treating disease, and in speeding up the repair of damaged and worn-out tissues.”

Genzyme, the manufacturer of Mozobil, received marketing approval last month from the FDA for the use of Mozobil in combination with G-CSF for the mobilization of hematopoietic stem cells in the treatment of non-Hodgkin’s lymphoma and multiple myeloma. According to John DiPersio, M.D., Ph.D., a professor at Washington University in St. Louis, “This product should become an integral part of the treatment regimen for transplantation because of the benefits it offers to patients, physicians and transplant centers.”

Professor Peter Weissberg, Medical Director at the British Heart Foundation, agrees. “It has long been known that the bone marrow contains cells that can replace lost or aged blood cells,” he explains. “It now seems increasingly likely that the bone marrow also contains cells that have the capacity to repair damaged internal organs, such as the heart and blood vessels, but that too few of them are released to be effective. This research has identified some important molecular pathways involved in mobilizing these cells. It may be possible to develop a drug that interacts with these pathways to encourage the right number and type of stem cells to enter the circulation and repair damage to the heart.”

Dr. Sara Rankin adds, “The body repairs itself all the time. However, when the damage is severe, there are limits to what it can do of its own accord. We hope that by releasing extra stem cells, as we were able to do in mice in our study, we could potentially call up extra numbers of whichever stem cells the body needs, in order to boost its ability to mend itself and accelerate the repair process. Mozobil is already out there on the market, so it’s feasible that trials could happen in the next five to ten years.”

Osiris Therapeutics, one of the leading biotech companies to develop clinical therapies from adult stem cells, announced today that it has completed patient enrollment in its phase III trial for the evaluation of Prochymal in the treatment of steroid-refractory acute Graft versus Host Disease (GvHD), which is a potentially fatal complication from bone marrow transplantation. Prochymal, one of the proprietary adult stem cell therapies developed by Osiris, is formulated exclusively from mesenchymal stem cells (MSCs), which are well known for their ability to prevent inflammation and scarring in addition to their capacity to regenerate tissue. A number of studies have already demonstrated MSCs to be effective in the treatment of GvHD, such as one study recently published in the Lancet in which Le Blanc et al. reported a 55% complete response rate from MSCs that were used in the treatment of steroid-resistant GvHD. Other studies have demonstrated a 58% complete response rate in pediatric patiens with end-stage GvHD, and phase II trials evaluating Prochymal have demonstrated a 77% complete resolution rate.

A total of 244 patients are now enrolled in the phase III trial, which is designed to assess both safety and efficacy of Prochymal over a 6-month period in a double-blinded, placebo controlled study that is coordinated among 72 leading bone marrow transplant centers across the United States, Canada, the United Kingdom, Spain, Italy, Germany, Switzerland and Australia. Among other places, these 72 medical centers in the U.S. include the Fred Hutchinson Cancer Research Center in Seattle, Washington, the M.D. Anderson Cancer Center in Houston, Texas, and the Karmanos Cancer Institute in Detroit, Michigan.

According to Dr. Paul Martin of the Fred Hutchinson Cancer Research Center, professor at the University of Washington and a lead investigator in the trial, “Completion of this study’s enrollment represents an outstanding accomplishment for the transplantation field. Steroid-refractory acute Graft versus Host disease poses one of the most serious and difficult to treat complications that can occur after bone marrow transplantation. Previous studies have not identified reliably effective treatments, and no drugs have been approved for this devastating disease. Transplant clinicians throughout the world now eagerly await results of this rigorous multicenter study.”

Thus far, 168 patients have been treated in the United States, 31 in Canada, 27 in Europe and 18 in Australia, which included a total of 27 pediatric patients. The last patient is expected to complete the trial in May of 2009.

As Dr. Moya Daniels, director for the GvHD program at Osiris, states, “On behalf of everyone at Osiris, I would like to offer our sincere appreciation to the patients, their families, and all of the outstanding healthcare professionals who participated in this historic event. We look forward with great anticipation to the results of this landmark stem cell trial and the opportunity to make a positive difference in the care of transplant patients everywhere.”

Prochymal has often been in the news lately, since Osiris and Genzyme announced a strategic alliance in November of this year for the development and commercialization of Prochymal. In the current phase III trial, which is evaluating Prochymal in patients who have failed to respond to corticosteroid treatment for acute GvHD, the key endpoints of this trial are complete response, as well as both 100-day and 180-day survival.

Osiris is also currently investigating Prochymal as a first-line agent for acute GvHD in a 184-patient phase III trial and as a therapy for Crohn’s disease in a 270-patient phase III trial. Prochymal is the only stem cell therapy currently designated by the FDA as both an Orphan Drug and a Fast Track product, and it is also being developed for the repair of heart tissue following a heart attack, and for the protection of pancreatic islet cells in patients with type 1 diabetes, and for the repair of lung tissue in patients with chronic obstructive pulmonary disease. Other adult stem cell therapies developed by Osiris and currently in their pipeline include Chondrogen which is being developed for a number of applications that include arthritis of the knee. The recent partnership between Osiris and Genzyme is geared for the development and commercialization of both Prochymal and Chondrogen in countries outside of the United States and Canada. In their intellectual property portfolio, Osiris has 47 U.S. patents, each with one or more foreign counterparts.